Bridging the data gaps in the epidemiology of hepatitis C virus infection in Malaysia using multi-parameter evidence synthesis

BACKGROUND: Collecting adequate information on key epidemiological indicators is a prerequisite to informing a public health response to reduce the impact of hepatitis C virus (HCV) infection in Malaysia. Our goal was to overcome the acute data shortage typical of low/middle income countries using statistical modelling to estimate the national HCV prevalence and the distribution over transmission pathways as of the end of 2009. METHODS: Multi-parameter evidence synthesis methods were applied to combine all available relevant data sources - both direct and indirect - that inform the epidemiological parameters of interest. RESULTS: An estimated 454,000 (95% credible interval [CrI]: 392,000 to 535,000) HCV antibody-positive individuals were living in Malaysia in 2009; this represents 2.5% (95% CrI: 2.2-3.0%) of the population aged 15-64 years. Among males of Malay ethnicity, for 77% (95% CrI: 69-85%) the route of probable transmission was active or a previous history of injecting drugs. The corresponding proportions were smaller for male Chinese and Indian/other ethnic groups (40% and 71%, respectively). The estimated prevalence in females of all ethnicities was 1% (95% CrI: 0.6 to 1.4%); 92% (95% CrI: 88 to 95%) of infections were attributable to non-drug injecting routes of transmission. CONCLUSIONS: The prevalent number of persons living with HCV infection in Malaysia is estimated to be very high. Low/middle income countries often lack a comprehensive evidence base; however, evidence synthesis methods can assist in filling the data gaps required for the development of effective policy to address the future public health and economic burden due to HCV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0564-6) contains supplementary material, which is available to authorized users

A [4Fe-4S]-Fe(CO)(CN)-L-cysteine intermediate is the first organometallic precursor in [FeFe] hydrogenase H-cluster bioassembly.

Biosynthesis of the [FeFe] hydrogenase active site (the 'H-cluster') requires the interplay of multiple proteins and small molecules. Among them, the radical S-adenosylmethionine enzyme HydG, a tyrosine lyase, has been proposed to generate a complex that contains an Fe(CO)2(CN) moiety that is eventually incorporated into the H-cluster. Here we describe the characterization of an intermediate in the HydG reaction: a [4Fe-4S][(Cys)Fe(CO)(CN)] species, 'Complex A', in which a CO, a CN- and a cysteine (Cys) molecule bind to the unique 'dangler' Fe site of the auxiliary [5Fe-4S] cluster of HydG. The identification of this intermediate-the first organometallic precursor to the H-cluster-validates the previously hypothesized HydG reaction cycle and provides a basis for elucidating the biosynthetic origin of other moieties of the H-cluster

The Novel Object and Unusual Name (NOUN) database: a collection of novel images for use in experimental research

Many experimental research designs require images of novel objects. Here we introduce the Novel Object and Unusual Name (NOUN) Database. This database contains 64 primary novel object images and additional novel exemplars for ten basic- and nine global-level object categories. The objects’ novelty was confirmed by both self-report and a lack of consensus on questions that required participants to name and identify the objects. We also found that object novelty correlated with qualifying naming responses pertaining to the objects’ colors. Results from a similarity sorting task (and subsequent multidimensional scaling analysis on the similarity ratings) demonstrated that the objects are complex and distinct entities that vary along several featural dimensions beyond simply shape and color. A final experiment confirmed that additional item exemplars comprise both sub- and superordinate categories. These images may be useful in a variety of settings, particularly for developmental psychology and other research in language, categorization, perception, visual memory and related domains

Nut production in Bertholletia excelsa across a logged forest mosaic: implications for multiple forest use

Although many examples of multiple-use forest management may be found in tropical smallholder systems, few studies provide empirical support for the integration of selective timber harvesting with non-timber forest product (NTFP) extraction. Brazil nut (Bertholletia excelsa, Lecythidaceae) is one of the world’s most economically-important NTFP species extracted almost entirely from natural forests across the Amazon Basin. An obligate out-crosser, Brazil nut flowers are pollinated by large-bodied bees, a process resulting in a hard round fruit that takes up to 14 months to mature. As many smallholders turn to the financial security provided by timber, Brazil nut fruits are increasingly being harvested in logged forests. We tested the influence of tree and stand-level covariates (distance to nearest cut stump and local logging intensity) on total nut production at the individual tree level in five recently logged Brazil nut concessions covering about 4000 ha of forest in Madre de Dios, Peru. Our field team accompanied Brazil nut harvesters during the traditional harvest period (January-April 2012 and January-April 2013) in order to collect data on fruit production. Three hundred and ninety-nine (approximately 80%) of the 499 trees included in this study were at least 100 m from the nearest cut stump, suggesting that concessionaires avoid logging near adult Brazil nut trees. Yet even for those trees on the edge of logging gaps, distance to nearest cut stump and local logging intensity did not have a statistically significant influence on Brazil nut production at the applied logging intensities (typically 1–2 timber trees removed per ha). In one concession where at least 4 trees ha-1 were removed, however, the logging intensity covariate resulted in a marginally significant (0.09) P value, highlighting a potential risk for a drop in nut production at higher intensities. While we do not suggest that logging activities should be completely avoided in Brazil nut rich forests, when a buffer zone cannot be observed, low logging intensities should be implemented. The sustainability of this integrated management system will ultimately depend on a complex series of socioeconomic and ecological interactions. Yet we submit that our study provides an important initial step in understanding the compatibility of timber harvesting with a high value NTFP, potentially allowing for diversification of forest use strategies in Amazonian Perù

Challenges and recent progress in drug discovery for tropical diseases

Infectious tropical diseases have a huge effect in terms of mortality and morbidity, and impose a heavy economic burden on affected countries. These diseases predominantly affect the world’s poorest people. Currently available drugs are inadequate for the majority of these diseases, and there is an urgent need for new treatments. This Review discusses some of the challenges involved in developing new drugs to treat these diseases and highlights recent progress. While there have been notable successes, there is still a long way to go.</p

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Developing Next-generation Brain Sensing Technologies - A Review.

Advances in sensing technology raise the possibility of creating neural interfaces that can more effectively restore or repair neural function and reveal fundamental properties of neural information processing. To realize the potential of these bioelectronic devices, it is necessary to understand the capabilities of emerging technologies and identify the best strategies to translate these technologies into products and therapies that will improve the lives of patients with neurological and other disorders. Here we discuss emerging technologies for sensing brain activity, anticipated challenges for translation, and perspectives for how to best transition these technologies from academic research labs to useful products for neuroscience researchers and human patients

Does oculomotor inhibition of return influence fixation probability during scene search?

Oculomotor inhibition of return (IOR) is believed to facilitate scene scanning by decreasing the probability that gaze will return to a previously fixated location. This “foraging” hypothesis was tested during scene search and in response to sudden-onset probes at the immediately previous (one-back) fixation location. The latencies of saccades landing within 1º of the previous fixation location were elevated, consistent with oculomotor IOR. However, there was no decrease in the likelihood that the previous location would be fixated relative to distance-matched controls or an a priori baseline. Saccades exhibit an overall forward bias, but this is due to a general bias to move in the same direction and for the same distance as the last saccade (saccadic momentum) rather than to a spatially specific tendency to avoid previously fixated locations. We find no evidence that oculomotor IOR has a significant impact on return probability during scene search

Combined Tevatron upper limit on gg->H->W+W- and constraints on the Higgs boson mass in fourth-generation fermion models

Report number: FERMILAB-PUB-10-125-EWe combine results from searches by the CDF and D0 collaborations for a standard model Higgs boson (H) in the process gg->H->W+W- in p=pbar collisions at the Fermilab Tevatron Collider at sqrt{s}=1.96 TeV. With 4.8 fb-1 of integrated luminosity analyzed at CDF and 5.4 fb-1 at D0, the 95% Confidence Level upper limit on \sigma(gg->H) x B(H->W+W-) is 1.75 pb at m_H=120 GeV, 0.38 pb at m_H=165 GeV, and 0.83 pb at m_H=200 GeV. Assuming the presence of a fourth sequential generation of fermions with large masses, we exclude at the 95% Confidence Level a standard-model-like Higgs boson with a mass between 131 and 204 GeV.We combine results from searches by the CDF and D0 collaborations for a standard model Higgs boson (H) in the process gg→H→W+W- in pp̅ collisions at the Fermilab Tevatron Collider at √s=1.96  TeV. With 4.8  fb-1 of integrated luminosity analyzed at CDF and 5.4  fb-1 at D0, the 95% confidence level upper limit on σ(gg→H)×B(H→W+W-) is 1.75 pb at mH=120  GeV, 0.38 pb at mH=165  GeV, and 0.83 pb at mH=200  GeV. Assuming the presence of a fourth sequential generation of fermions with large masses, we exclude at the 95% confidence level a standard-model-like Higgs boson with a mass between 131 and 204 GeV.Peer reviewe

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.